SERPINE2 encodes a serine protease inhibitor that plays diverse roles in tissue homeostasis and disease pathogenesis. The protein functions as an inhibitor of serine proteases including thrombin, trypsin, and urokinase, and possesses heparin-binding activity 1. In fibrotic diseases, SERPINE2 demonstrates context-dependent effects: it acts as an anti-fibrotic factor in pulmonary fibrosis, where it is associated with pro-resolving fibroblast neighborhoods and functionally modulates human lung fibrosis 2, while in hepatic stellate cells, it promotes fibroblast activation through YAP/TAZ-mediated mechanosignaling pathways 3. SERPINE2 exhibits oncogenic properties in multiple cancer types, promoting metastasis in liver cancer by inhibiting EGFR ubiquitination and degradation through competition with c-Cbl E3 ligase, thereby maintaining EGFR protein stability and downstream signaling 4. Similarly, in renal cell carcinoma, SERPINE2 promotes cell growth, invasion, and epithelial-mesenchymal transition 5. In vascular dementia, reduced SERPINE2-LRP1 signaling enhances oligodendrocyte progenitor cell differentiation and promotes tissue repair 1. The gene shows expression in inflammatory contexts, being upregulated in degenerated intervertebral disc cells alongside other inflammatory mediators 6. Genetic association studies suggest potential links to COPD susceptibility, though meta-analyses show inconsistent results 78.